In a phase IIa study reported in The Lancet Oncology, Escrivá-de-Romani et al evaluated whether the chemotherapy-free triplet of the HER2-targeted bispecific antibody zanidatamab plus palbociclib and fulvestrant showed activity in heavily pretreated patients with hormone receptor (HR)-positive, HER2-positive advanced unresectable or metastatic breast cancer.
Study Details
In the study, 51 patients from sites in Spain, Canada, and the United States were enrolled between June 2020 and October 2022 (8 in part 1, 43 in part 2). In part 1, patients received a starting regimen of zanidatamab 20 mg/kg once every 2 weeks on days 1 and 15 of a 28-day cycle with palbociclib 125 mg once daily on days 1–21 of each cycle and fulvestrant 500 mg once every 2 weeks for the first three doses and then once every 4 weeks. In part 2, patients received recommended doses of the triple regimen. Patients had a median of four previous HER2-targeted therapies. The primary efficacy outcome measure was 6-month progression-free survival.
Key Findings
The part 1 starting regimen was confirmed as the recommended dose regimen for part 2. All 51 patients received the recommended regimen and were evaluable for safety and efficacy.
Median follow-up was 16.1 months (interquartile range = 9.9–23.4 months). Among the 51 patients, 6-month progression-free survival was 66.7% (95% confidence interval [CI] = 52.1%–79.2%). Median progression-free survival was 11.7 months (95% CI = 8.4–14.9 months). The confirmed objective response rate was 34.8% among 46 patients with measurable disease, with complete response in 3 patients (7%). Median duration of response was 14.8 months (95% CI = 11.6–24.7 months). Disease control rate was 91.3%.
All 51 patients had at least one treatment-related adverse event of any grade, most commonly diarrhea (80%, 67% grade 1 or 2). Grade 3 or 4 treatment-related adverse events occurred in 34 patients (67%), most commonly neutropenia (51%). A serious grade 3 treatment-related adverse event occurred in 1 patient (elevated transaminases). No treatment-related deaths were reported.
The investigators concluded: “Zanidatamab plus palbociclib and fulvestrant was generally safe and showed promising antitumour activity, supporting further evaluation of this chemotherapy-free triplet regimen.”
Santiago Escrivá-de-Romani, MD, Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Zymeworks, Jazz Pharmaceuticals, and Pfizer. For full disclosure of all study authors, visit The Lancet Oncology.
